白虎加桂枝汤对高尿酸血症并急性痛风性关节炎大鼠抗炎作用机制探究
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摘要
目的:探索白虎加桂枝汤对高尿酸血症并急性痛风性关节炎(HUA+AUG)治疗作用及抗炎机制。方法:雄性SD大鼠60只根据体质量随机分为:正常组、模型组、白虎加桂枝汤低剂量组(0.265g/100g),白虎加桂枝汤中剂量组(0.53g/100g),白虎加桂枝汤高剂量组(1.06g/100g),秋水仙碱组(0.05mg/100g)。连续给药7d,第4天构建急性痛风性关节炎模型。观察大鼠一般情况,检测大鼠血清UA、CRP、NLRP3、NF-κB、Caspase-1、TNF-α、IL-6、IL-1、IL-10指标,踝关节组织中NLRP3、Caspase-1、TNF-α、NF-κB蛋白的表达,观测关节肿胀度,进行步态观察,炎症指数评分及大鼠踝关节滑膜形态学观察。结果:白虎加桂枝汤可以减轻HUA+AUG大鼠模型关节肿胀度,改善步态及炎症评分,降低血清CPR,同时还能降低血清NLRP3、Caspase-1、NF-κB、TNF-α、IL-6、IL-1水平,升高血清中IL-10水平;降低踝关节组织中NLRP3、Caspase-1、TNF-α、NF-κB蛋白的表达。结论:白虎加桂枝汤具有治疗HUA+AUG的作用,其机制可能与抑制NLRP3炎性体激活,抑制炎症反应有关。
Objective: To explore the therapeutic effect and anti-inflammatory mechanism of Baihu Jiaguizhi Decoction on hyperuricemia and acute gouty arthritis(HUA+AUG). Methods: Sixty male Sprague-Dawley rats were randomly divided into normal group, model group, Baihu Jiaguizhi Decoction low dose group(0.265 g/100 g), Baihu Jiaguizhi Decoction medium dose group(0.53 g/100 g). Baihu Jiaguizhi Decoction high dose group(1.06 g/100 g) and colchicine group(0.05 mg/100 g). The acute gouty arthritis model was constructed on day 4 for 7 days of continuous administration. The general condition of rats was observed. To detected the serum UA, CRP, NLRP3, NF-κB, Caspase-1, TNF-α, IL-6, IL-1, IL-10 indicators, and the expression of NLRP3, Caspase-1, TNF-α, NF-κB protein in ankle joint tissue. To observe the degree of joint swelling, and the gait, inflammation index score and morphological observation of rat ankle synovium. Results: Baihu Jiaguizhi Decoction could reduce joint swelling in HUA+AUG rat model, improve gait and inflammation score, reduce serum CPR, and reduce serum NLRP3, Caspase-1, NF-κB, TNF-α, IL-6, IL-1 level, increase serum IL-10; reduce the expression of NLRP3, Caspase-1, TNF-α, NF-κB protein in ankle joint tissue. Conclusion: Baihu Jiaguizhi Decoction has the effect of treating HUA+AUG, and its mechanism may be related to inhibiting NLRP3 inflammasome activation and inhibiting inflammatory response.
Objective: To explore the therapeutic effect and anti-inflammatory mechanism of Baihu Jiaguizhi Decoction on hyperuricemia and acute gouty arthritis(HUA+AUG). Methods: Sixty male Sprague-Dawley rats were randomly divided into normal group, model group, Baihu Jiaguizhi Decoction low dose group(0.265 g/100 g), Baihu Jiaguizhi Decoction medium dose group(0.53 g/100 g). Baihu Jiaguizhi Decoction high dose group(1.06 g/100 g) and colchicine group(0.05 mg/100 g). The acute gouty arthritis model was constructed on day 4 for 7 days of continuous administration. The general condition of rats was observed. To detected the serum UA, CRP, NLRP3, NF-κB, Caspase-1, TNF-α, IL-6, IL-1, IL-10 indicators, and the expression of NLRP3, Caspase-1, TNF-α, NF-κB protein in ankle joint tissue. To observe the degree of joint swelling, and the gait, inflammation index score and morphological observation of rat ankle synovium. Results: Baihu Jiaguizhi Decoction could reduce joint swelling in HUA+AUG rat model, improve gait and inflammation score, reduce serum CPR, and reduce serum NLRP3, Caspase-1, NF-κB, TNF-α, IL-6, IL-1 level, increase serum IL-10; reduce the expression of NLRP3, Caspase-1, TNF-α, NF-κB protein in ankle joint tissue. Conclusion: Baihu Jiaguizhi Decoction has the effect of treating HUA+AUG, and its mechanism may be related to inhibiting NLRP3 inflammasome activation and inhibiting inflammatory response.
引文
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[13]华亮,周蜜,何琴花,等.清热除湿通络法对大鼠痛风性关节炎模型中NALP3炎性体表达的影响.中华中医药杂志,2018,33(4):1591-1594
[14]周永学,李敏,唐志书,等.中药石膏及其主要成分解热抗炎作用及机制研究陕西中医学院学报,2012,35(5):74-76
[15]徐锋.基于NLRP3炎症小体通路桂枝抗炎有效部位抗炎作用机制研究.成都:成都中医药大学,2017
[16]雷霞,董文婷,笔雪艳,等.知母各化学拆分组分的抗炎及免疫调节活性.中药材,2015,38(9):1904-1907
[2]中华医学会内分泌学分会.高尿酸血症和痛风治疗中国专家共识.中华内分泌代谢杂志,2013,29(11):913-920
[3]Kuo C F,Grainge M J,Zhang W,et al.Global epidemiology of Gout:prevalence,incidence and risk factors.Nat Rev Rheumatol,2015,11:649-662
[4]Coderre T J,Wall P D.Ankle joint urate arthritis(AJUA)in rats:An alternative animal model of arthritis to that produced by Freund’s adjuvant.Pain,1987,28(3):379
[5]Coderre T J,Wall P D.Ankle joint urate arthritis in rats provides a useful tool for the evaluation of analgesic and anti-arthritic agents.Pharmacology Biochemistry&Behavior,1988,29(3):461
[6]吕军,吕芳,方和金,等.高尿酸血症并急性痛风性关节炎大鼠模型的建立.中国现代医学杂志,2013,23(27):11-16
[7]Martinon F,Mayor A,Jürg Tschopp.The Inflammasomes:Guardians of the Body.Annual Review of Immunology,1912,27(27):229-265
[8]Ru L B.Intracellular innate immunity in gouty arthritis:Role of NALP3 inflammasome.Immunology&Cell Biology,2010,88(1):20-23
[9]Fernandes J C,Martelpelletier J,Pelletier J P.The role of cytokines in osteoarthritis pathophysiology.Biorheology,2002,39(1-2):237-246
[10]赵计轩,张榜,崔炎.当代名老中医诊辨痛风经验总结.时珍国医国药,2017,28(3):748-750
[11]上海市卫生局.上海市中医病证诊疗常规.2版.上海:上海中医药大学出版社,2003:92-93
[12]王挺挺,朱红,张茂华.白虎加桂枝汤合四妙丸治疗急性痛风性关节炎疗效分析.新中医,2016(1):63-64
[13]华亮,周蜜,何琴花,等.清热除湿通络法对大鼠痛风性关节炎模型中NALP3炎性体表达的影响.中华中医药杂志,2018,33(4):1591-1594
[14]周永学,李敏,唐志书,等.中药石膏及其主要成分解热抗炎作用及机制研究陕西中医学院学报,2012,35(5):74-76
[15]徐锋.基于NLRP3炎症小体通路桂枝抗炎有效部位抗炎作用机制研究.成都:成都中医药大学,2017
[16]雷霞,董文婷,笔雪艳,等.知母各化学拆分组分的抗炎及免疫调节活性.中药材,2015,38(9):1904-1907